Abstract
The use of viruses as transneuronal tracers has become an increasingly powerful technique for defining the synaptic organization of neural networks. Although a number of recombinant alpha herpesviruses are known to spread selectively in the retrograde direction through neural circuits only one strain, the H129 strain of herpes simplex virus type 1, is reported to selectively spread in the anterograde direction. However, it is unclear from the literature whether there is an absolute block or an attenuation of retrograde spread of H129. Here, we demonstrate efficient anterograde spread, and temporally delayed retrograde spread, of H129 and three novel recombinants. In vitro studies revealed no differences in anterograde and retrograde spread of parental H129 and its recombinants through superior cervical ganglion neurons. In vivo injections of rat striatum revealed a clear bias of anterograde spread, although evidence of deficient retrograde transport was also present. Evidence of temporally delayed retrograde transneuronal spread of H129 in the retina was observed following injection of the lateral geniculate nucleus. The data also demonstrated that three novel recombinants efficiently express unique fluorescent reporters and have the capacity to infect the same neurons in dual infection paradigms. From these experiments we conclude that H129 and its recombinants not only efficiently infect neurons through anterograde transneuronal passage, but also are capable of temporally delayed retrograde transneuronal spread. In addition, the capacity to produce dual infection of projection targets following anterograde transneuronal passage provides an important addition to viral transneuronal tracing technology.
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Acknowledgments
This research was supported by NIH grants P40 RR018604 and PEW 2010-000225-002 post-doctoral fellowship to EAE. We thank Dr. Nicholas Brecha for critical evaluation of the retinal data, Vivian Allahyari for technical assistance with the animal studies, Beate Sodeik for providing the HSV-1 BAC used to produce H129-424, Jessica Brooks for assistance in construction of H129-772, and Stuart Mazzone for providing the plasmid used to construct the H129-772 recombinant. Santiago Rompani provided essential preliminary insights into H129 transport that were instrumental in the inclusion and design of the visual system experiments.
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G. J. Wojaczynski and E. A. Engel contributed equally to this study.
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Wojaczynski, G.J., Engel, E.A., Steren, K.E. et al. The neuroinvasive profiles of H129 (herpes simplex virus type 1) recombinants with putative anterograde-only transneuronal spread properties. Brain Struct Funct 220, 1395–1420 (2015). https://doi.org/10.1007/s00429-014-0733-9
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DOI: https://doi.org/10.1007/s00429-014-0733-9